Project Summary/Abstract: Improved bone health and the subsequent reduction in fracture risk represents a significant health intervention, improving longevity as well as quality of life in aging populations. The development of ?anabolic? agents that can promote the rebuilding of lost bone mass would represent a significant impact on the field and on the treatment of bone disease. We have engineered a bio-active silica based nanoparticle capable of promoting osteoblast differentiation and mineralization while inhibiting osteoclastogenesis and therefore these nanoparticles have the potential to promote new bone formation while simultaneously reducing bone breakdown. The goals of this study are to further investigate these novel nanoparticles for the treatment of systemic bone disease. The studies proposed herein will test the hypothesis that engineered silica based nanoparticles represent a novel therapeutic agent capable of preventing and/or reversing bone loss in a pre- clinical model of post-menopausal bone loss. We will investigate the optimal method of administration as well as attempt to increase efficacy through bone targeting surface properties. Endpoints include a quantitation of nanoparticle absorption relevant to route of administration, quantitative and qualitative analysis of bone metabolism and serum markers. Additionally, we will utilize a reporter mouse to assess the possibility that the nanoparticles work in part by stimulation of autophagy.